We will study quantitative and qualitative alterations in the control of immunoglobulin (lg) secretion in the central nervous system (CNS) as reflected in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). We will study the in vitro capacity of CSF lymphocytes to differentiate into immunoglobulin secreting cells (lgSC) and compare these responses to the blood cell responses of the same subject. The amount of secreted lg will be quantitated and analyzed for spectrotype pattern. CSF T-cells will be expanded using T-cell growth factor and the regulatory effect of these cells on lg secretion by blood B-cell studied. The capacity of CSF and eluates from CNS lesions to stimulate B-cell differentiation will be studied and compared to other neurologic diseases. Increased knowledge of the mechanisms underlying altered lg secretion in the CNS will enhance our understanding of alterations in immune responsiveness in MS and may help establish a link between such alterations and the pathogenesis of MS.